Clinically significant respiratory disease that requires mechanical ventilation support or 50% oxygen.
Active, uncontrolled infection, or active systemic illness that requires ongoing vasopressor support or mechanical ventilation
Requiring mechanical ventilation
Subjects requiring vasopressor or mechanical ventilation.
Pulmonary failure (requiring mechanical ventilation) not due to active LCH.
Adequate respiratory function defined as not requiring supplemental oxygen or mechanical ventilation; oxygen saturation 90% or higher on room air
RETREATMENT WITH MODIFIED T-CELLS EXCLUSION CRITERIA: Patient requiring supplemental oxygen or mechanical ventilation
Requirement for mechanical ventilation within 7 days prior to Day 1, or sustained oxygen delivery for > 24 hours within 7 days prior to Day 1, or any oxygen requirement within 48 hours prior to Day 1
Adequate respiratory function defined as not requiring supplemental oxygen or mechanical ventilation; oxygen saturation 90% or higher on room air
Adequate respiratory function defined as not requiring supplemental oxygen or mechanical ventilation; oxygen saturation 90% or higher on room air
Adequate respiratory function defined as not requiring supplemental oxygen or mechanical ventilation; oxygen saturation 90% or higher on room air
Subject does not require supplemental oxygen or mechanical ventilation, and oxygen saturation by pulse oximetry is 94% or higher on room air.
Require mechanical ventilation or vasopressors for hemodynamic support at the time of randomization.
Not requiring supplemental oxygen or mechanical ventilation; oxygen saturation 90% or higher on room air; no dyspnea at rest
ELIGIBILITY CRITERIA FOR T-CELL PRODUCT INFUSION: Not requiring supplemental oxygen or mechanical ventilation, oxygen saturation 90% or higher on room air and no dyspnea at rest
RETREATMENT WITH MODIFIED T CELLS: Patient requiring supplemental oxygen or mechanical ventilation
Endotracheal intubation and mechanical ventilation at any FiO2
ELIGIBILITY CRITERIA TO UNDERGO OPTIONAL T CELL ABLATION\r\n* Research participant has >= 1% CAR T cells in the peripheral blood\r\n* Pulmonary: not requiring supplemental oxygen or mechanical ventilation, oxygen saturation 90% or higher on room air\r\n* Cardiovascular: not requiring pressor support, no symptomatic cardiac arrhythmias, no acute coronary syndrome, or uncontrolled hypertension\r\n* Renal Function: serum creatinine did NOT increase by more than 2.5 fold from baseline (at time of screening)\r\n* Liver Function: adequate liver function defined as total bilirubin =< 3.0 mg/dl \r\n* AST =< 5 x ULN, ALT =< 5 x ULN\r\n* Neurological: research participant without clinically significant encephalopathy/new focal deficits\r\n* Infectious diseases: no clinical evidence of uncontrolled active infectious process
Not requiring supplemental oxygen or mechanical ventilation, oxygen saturation 90% or higher on room air
(ELIGIBILITY CRITERIA AT TIME OF INFUSION OF GENETICALLY MODIFIED AUTOLOGOUS T CELLS): Not requiring supplemental oxygen or mechanical ventilation, oxygen saturation 90% or higher on room air
Not requiring supplemental oxygen or mechanical ventilation, oxygen saturation 90% or higher on room air
Pulmonary: not requiring supplemental oxygen or mechanical ventilation, oxygen saturation 90% or higher on room air
Pulmonary criteria: not requiring supplemental oxygen or mechanical ventilation, oxygen saturation 90% or higher on room air
Require mechanical ventilation or vasopressors for hemodynamic support at the time of enrollment.
Clinically significant respiratory disease that requires mechanical ventilation support or 50% oxygen.
Patients on mechanical ventilation.
Not requiring supplemental oxygen or mechanical ventilation, oxygen saturation 90% or higher on room air
Mechanical ventilation, renal replacement therapy, admitted in intensive care until at time of enrollment
Has been on mechanical ventilation for > 28 days
Currently on invasive mechanical ventilation or noninvasive positive pressure ventilation (CPAP or bilevel positive airway pressure) or requiring > 2LPM supplemental oxygen therapy to maintain O2 saturation > 90% due to hypoxemia
Oxygenation index (OI) > 13, but < 37, for two consecutive blood gases which should be separated by at least one hour within 48 hours of the initiation of mechanical ventilation.
Respiratory failure requiring mechanical ventilation or non-invasive ventilation
Requiring mechanical ventilation
Requires mechanical ventilation or is hemodynamically unstable at the time of randomization
Respiratory failure requiring greater than 6 Lpm supplemental oxygen (O2) by nasal cannula or mechanical ventilation within the past six weeks
Severe dyspnea at rest, due to complications of advanced malignancy, or requiring supplementary oxygen therapy.
Severe dyspnea at rest due to complications of advanced malignancy or requiring supplementary oxygen therapy
Severe dyspnea at rest due to complications of advanced malignancy or current requirement for continuous oxygen therapy
Severe dyspnea at rest due to complications of advanced malignancy, or requiring supplementary oxygen therapy.
Receiving supplementary continuous oxygen
Dyspnea at rest due to complications of advanced malignancy or other disease requiring continuous oxygen therapy.
Current dyspnea at rest of any origin, or other diseases requiring continuous oxygen therapy.
Dyspnea at rest or other diseases that require continuous oxygen therapy
Severe dyspnea at rest due to complications of advanced malignancy or requiring current continuous oxygen therapy
Current dyspnea at rest, owing to complications of advanced malignancy or any requirement for supplemental oxygen to perform activities of daily living
History of interstitial lung disease or pneumonitis requiring supplemental oxygen or treatment with oral or intravenously administered corticosteroids
Subjects who need daily oxygen therapy
Patients requiring any daily supplemental oxygen
Subject requires continuous supplemental oxygen for any reason. Additional Exclusion Criteria for Arm B
Requirement for daily supplemental oxygen
Clinically significant pulmonary compromise, including a requirement for supplemental oxygen use to maintain adequate oxygenation.
Dependence on continuous supplemental oxygen use
Chronic bronchitis or emphysema requiring oxygen therapy within the last 6 months
Clinically significant pulmonary compromise, including a requirement for supplemental oxygen use to maintain adequate oxygenation.
Participant has a need for supplemental oxygen with the exception of using previously existing non-invasive continuous positive airway pressure (CPAP) at night.
Subjects with a history of interstitial lung disease; patients requiring continuous supplemental oxygen are excluded to avoid possible complications from pneumonitis
ARM 2 - A: Pulmonary: patients with a requirement for supplemental oxygen or evidence of moderate-severe COPD by PFTs are permitted to enroll
Patients with baseline respiratory insufficiency severe enough to require supplemental oxygen.
Patients requiring ventilator support or oxygen supplementation exceeding 40% fraction of inspired oxygen (FiO2) within 14 days of enrollment.
Research participant requires supplemental oxygen to keep saturation greater than 95% and the situation is not expected to resolve within 2 weeks
Research participant does not require supplemental oxygen to keep saturation greater than 95% and/or does not have presence of any radiographic abnormalities on chest x-ray that are progressive
Patients/subjects who need daily oxygen therapy
Daily use of oxygen supplementation.
Clinically-significant pulmonary compromise, including a requirement for supplemental oxygen use to maintain adequate oxygenation
FOR ALL PHASES (Ib AND II): Chronic oxygen therapy
Oxyhemoglobin saturation at rest >= 95% (off supplemental oxygen)
Use of continuous oxygen
Patients/subjects who need daily oxygen therapy
Patients requiring oxygen therapy
Patients requiring oxygen therapy
Patients requiring continuous supplemental oxygen are excluded to avoid possible complications from pneumonitis
Need for supplemental oxygen
No supplemental oxygen requirement
Patient is on supplemental home oxygen
ADDITIONAL CRITERIA FOR STUDY CONTINUATION: Patient is on supplemental home oxygen
Research participant does not require supplemental oxygen to keep saturation greater than 95% and/or does not have presence of any radiographic abnormalities on chest x-ray that are progressive
Research participant requires supplemental oxygen to keep saturation greater than 95% and the situation is not expected to resolve within 2 weeks
Continuous oxygen use
Within 14 days of study registration: No oxygen requirement on room air or requiring =< 2L supplemental oxygen (O2)
Current use of supplemental oxygen
Clinically-significant pulmonary compromise, including a requirement for supplemental oxygen use to maintain adequate oxygenation.
Idiopathic pulmonary fibrosis or other severe interstitial lung disease that requires oxygen therapy or is thought to require oxygen therapy within 1 year prior to step 1 registration
Any patient requiring supplemental oxygen therapy
Respiratory insufficiency with oxygen requirement > 4 L nasal cannula
Patients must not require daily supplemental oxygen
No history of severe chronic obstructive pulmonary disease (COPD) or emphysema or interstitial lung disease currently on home supplemental oxygen; patients with NSCLC with stable COPD or emphysema not requiring supplemental oxygen are eligible
No requirement for supplemental oxygen therapy
Severe hypoxemia with room air pulmonary arterial oxygen tension (PaO2) < 70, supplemental oxygen dependence, or DLCO < 50% predicted
Patients requiring supplemental oxygen
Participants requiring any daily supplemental oxygen
Known severely impaired lung function, including: • CTCAE grade 2 (or greater) hypoxia (decreased oxygen saturation with exercise [e.g., pulse oximeter <88%]; intermittent supplemental oxygen)
Patients requiring supplemental oxygen therapy
Patient is on supplemental home oxygen
Patients with pulmonary disease limiting daily function or requiring oxygen supplementation
Patients on supplemental home oxygen
Continuous oxygen use
Patients on oxygen
May not be on supplemental oxygen
Patient must not have a requirement for supplemental oxygen
The patient must not be dependent on supplemental oxygen
Use of formalin or hyperbaric oxygen treatment
Requirement of supplemental oxygen.
History of interstitial pneumonitis and/or require supplemental oxygen therapy
Requiring supplemental oxygen at more than 2 L/min
Dyspnea of any cause requiring supplemental oxygen therapy;
Participants requiring any daily supplemental oxygen
Patients with history of lung disease currently requiring any pharmacologic or supplemental oxygen treatment
Adequate pulmonary function defined as:\r\n* No dyspnea at rest\r\n* No known requirement for supplemental oxygen\r\n* No known active pneumonitis
Clinically significant pulmonary hypertension, as defined by the requirement for ongoing pharmacologic treatment or the consistent or intermittent use of supplemental home oxygen.
Cohort A: Continuous oxygen use
Patient currently requiring supplemental oxygen for his/her daily life
Requirement for supplemental oxygen to carry out activities of daily living
Patients with active infection defined as:\r\n* Positive blood culture within 48 hours of study registration\r\n* Need for supplemental oxygen or vasopressors within 48 hours of study entry
Oxygen saturation <95% on room air by trans-cutaneous method or need for any supplemental oxygenation or ventilatory support, or increase in oxygen supplementation requirement of ?2 litres for subjects with chronic oxygen dependency. For those subjects with a history of chronic hypoxia (without supplemental oxygen), an oxygen saturation of at least 3% below the patient's historical baseline oxygen saturation will satisfy this criterion.
Oxygen saturation < 90% despite supplemental oxygen > 6 L/minute.
Are receiving chronic oxygen therapy
Daily supplemental oxygen
Subjects currently on supplemental oxygen support
Patients with history of lung disease currently requiring any pharmacologic or supplemental oxygen treatment
Chronic supplemental oxygen requirement or hypoxemia < 92% blood oxygen saturation (SpO2)
Any patients requiring oxygen at baseline
Currently requiring high flow oxygen for oxygenation
Supplemental oxygen dependency
Patients must be able to walk unassisted without oxygen
Supplemental oxygen requirement > 6 L per minute
Patients requiring oxygen more than 2 liters
No requirement for supplemental oxygen (O2)
Patients with history of lung disease currently requiring any supplemental oxygen treatment
Clinically significant pulmonary compromise (e.g. require supplemental oxygen)
Adequate pulmonary function as assessed by oxygen saturation >= 90% when ambulating and not requiring supplemental oxygen
Respiratory disease requiring continuous supplemental oxygen
Supplemental oxygen requirement > 6 L per minute
Supplemental oxygen requirement > 6 L per minute
Oxygen saturation < 90% despite supplemental oxygen > 6 L/min
On chronic oxygen
Severe hypoxemia with room air partial pressure of oxygen (PaO2) < 70, supplemental oxygen dependence, or DLCO < 50% predicted
Hypoxemia (less than 90% saturation with supplemental oxygen)
Current use of supplemental oxygen
Significant valvular disease, or significant pulmonary disease requiring supplemental oxygen therapy
Patients that require supplemental oxygen are excluded
Patients requiring continuous supplemental oxygen due to the requirement of spirometry during all imaging studies
Patients with history of lung disease currently requiring any pharmacologic or supplemental oxygen treatment
Requires daily supplemental oxygen.
Patients that require supplemental oxygen are excluded
Oxygen saturation >= 90% when ambulating and not requiring supplemental oxygen